The identification of viral specific mechanisms which could be tarted for the prevention or treatment of viral infectious in the central nervous system are the main goals of our studies. Infections by enveloped RNA viruses, such as measles, rabies, HIV- 1, HTLV-1, share common strategies with respect to viral entry and, to some extent, viral assembly. Many enveloped viruses are RNA viruses and replicate by using virus encoded RNA-dependent RNA polymerase or reverse transcriptases. All of these phases in the viral replication cycle could potentially be targeted specifically without affecting the viability and functions of the host cell. In order to identify specific in detail and on the molecular level, our efforts have focused on the replication and cytopathogeneicity of negative strand RNA viruses. With respect to viral replication, we have studied the components of the multifunctional polymerase complex of vesicular stomaitis virus (VSV) and, in particular, the L protein and the phosphoprotein NS. The mapping of monoclonal antibodies directed against the NS protein suggested a potential heterogeneity in the antigenicity of the amino terminal half of the protein, which may be the result of the large number of different phosphorylation patterns of this region. Expression of the phosphoprotein in a eukaryotic and prokaryotic system did not affect the aberrant migration of the protein on polyacrylamide gels, suggesting a linear rather than a globular structure, which enables it to mediate the binding of the large catalytic protein subunit L to its ribonucleocapsid template. VSV transcription is regulated by the viral M protein which binds to the template and thereby arrests the polymerase. We have shown that phosphorylation of protein M by the cellular protein kinase C can stimulate viral transcription may occur during he uncoating of the virus upon entry into the cell. Studies on the potential role of protein kinases during the entry of HIV-1 into CD4 receptor-expressing host cells have currently been initiated, together with studied on the pseudotype formation between VSV and HIV-1. The VSV M protein plays a central role in viral assembly. Expressed by itself it may also cause cytopathic effects, possibly by inducing a disorganization of cytoskeletal elements. Studies on the role of protein M in both viral assembly and cytopathogenicity are in progress.